Phyllanthus amarus is an herb for the treatment of various ailments including malaria. Its antiplasmodial properties and antioxidant capacity have been reported, but very little is known about its effect on CD36 in relation to hepatic insulin resistance and triacylglycerol level. Hence, this study was undertaken to evaluate the changes in soluble CD36 concentrations and correlation with hepatic insulin resistance index and triacylglycerol levels in liver of Plasmodium berghei malarial parasite infected mice treated with graded doses of Phyllanthus amarus ethanolic leaf extract. Thirty (30) adult Swiss albino mice of both sexes weighing between 20-30g were assigned into six (6) groups (n=5/grp). Crude ethanolic leaf extract of Phyllanthus amarus was administered at 150, 300 and 450mg/kg/d as single daily dose for 7 days. On the 8th day of study, the mice were sacrificed under chloroform anaesthesia after an overnight fast. Blood sample was collected by cardiac puncture and centrifuged to obtain serum which was used for the assay of serum CD36, glucose and insulin, while, liver of each mouse was excised and processed for the assay of varying doses (150, 300 and 450mg/kg/d) of Phyllanthus amarus crude ethanolic leaf extract to experimental mice infected with P. berghei malarial parasite for seven days maintained serum soluble CD36 (3.40±0.52pg/ml, 3.47±0.46pg/ml and 3.37±0.46pg/ml), hepatic insulin resistance index (0.85±0.10, 0.77±0.17 and 0.82±0.13) and liver triacylglycerol (134.33±15.95mg/dl, 174.00±11.27mg/dl and 163.67±11.02mg/dl) levels, respectively, in trends that compared well with the Control and chloroquine – treated data ( C D 3 6 = 3.03±0.12pg/ml, liver TAG = 139.33±12.01, HIR index = 0.64±0.07). Correlation of CD36 with liver triacylglycerol for the malarial infected group without treatment was strongly positive, while, that with hepatic insulin resistance index was strongly negative. The control and chloroquine treated groups produced similar correlation pattern, but those for the extract-treated were weaker. Malarial infection in experimental mice significantly (p<0.05) increased serum soluble CD36 and this impacted HIR index and liver TAG. However, extract and chloroquine treatments ameliorated the malaria-induced level of serum soluble CD36 and hepatic triacylglycerol, using documented methods. Results indicate that infection of mice with Plasmodium berghei malarial parasite yielded significant increase in level of CD36 (5.40±0.70pg/ml) and liver triacylglycerol, TAG (259.00±7.21mg/dl), but abnormal reduced (p<0.05) hepatic insulin resistance, HIR index (0.37±0.05) when compared with the control mice (CD36 = 3.47±0.46pg/ml, liver TAG = 161.00±10.00, HIR index = 0.68±0.18) at the 5% probability level. However, administration of as starting materials for drugs (Sofowora, 1993). Plants have provided an alternative strategy in research for new drugs. It is likely that plants will continue to be a valuable source of new molecules which may after possible chemical manipulations provide new and improved drugs (Shan et al., 2006). One of such plants is Phyllanthus amarus.Phyllanthus amarus belongs to the family Euphorbiaceae (the spurge family) from which the largest genus is the Euphorbia. It has about eight hundred (800) species which are found in tropical and subtropical countries of the world (Mazumder et al., 2005). Phytochemicals identified in the leaf extract include alkaloids, flavonoids, tannins, saponins, anthraquinone and glycosides (Onyesom et al., 2015). The antimalarial activity of P. amarus has been observed (Onyesom and Adu, 2015). Malaria is a mosquito borne infectious disease of humans caused by eukaryotic protists of the genus Plasmodium. It is widespread in tropical and subtropical regions of the world including much of the sub-Saharan Africa. In Nigeria, malaria is mostly caused by Plasmodium falciparum. The association with HIR index and liver TAG in manners that were similar to the control trend.