The present study investigates gender dependent effects of insulin resistance on lipid profile and adipocytokines in individuals with diabetes receiving oral antidiabetic drugs (OADs). The aim was also to reveal the changes in the expression of genes involved in lipid metabolism and inflammation. Lipid profile, adipocytokine levels and homeostatic model assessment of insulin resistance (HOMA-IR) was assessed in 100 patients with diabetes (M = 43, F = 57) matched for age and gender with healthy individuals (M = 45, F = 55). The expression pattern of genes was analyzed by quantitative real time PCR. Males consuming metformin with other drugs exhibited a positive association between HOMA-IR and cholesterol, triglyceride and very low density lipoprotein (VLDL). Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin. In males and females with diabetes, a comparable expression of peroxisome proliferator activated receptor γ (PPARγ) while higher expression of sterol regulatory element binding protein 1 (SREBP1) was observed. Expression of fatty acid synthase (FAS), long chain acyl CoA Synthetases (ACSL), malonyl-CoA-acyl carrier protein transacylase (MCAT) and nuclear factor kappa β (NFkβ) was higher in men with diabetes than healthy males. Expression of tumor necrosis factor α (TNF-α) was higher in males and females with diabetes than respective healthy genders. Insulin resistance adversely affects lipid profile, adipocytokines in males with type 2 diabetes. Expression of genes involved in lipid metabolism and inflammation is found to be undesirably and differentially altered in both the genders.