Objective To investigate the effects of interleukin-6 (IL-6) on mitochondrial biogenesis in activated astrocytes (AS) and the role of adenosine monophosphate protein kinase (AMPK) in this process. Methods The AS isolated from neonatal rat cerebral codex were purified and cultured.The AS was randomly divided into 5 groups: control group, lipopolysaccharide(LPS)+ interferon-γ(IFN-γ) group(IFN-γ group), LPS+ IFN-γ+ IL-6 group(IL-6 group), LPS+ IFN-γ+ IL-6R siRNA+ IL-6 group(siRNA group), and LPS+ IFN-γ+ negative control(NC)+ IL-6 group(NC group), then, AS in each group was treated for 6 h. Tumor necrosis factor-α(TNF-α)mRNA and interleukin-1β(IL-1β)mRNA expression were detected by adopting reverse transcription-polymerase chain reaction (RT-PCR). The levels of reactive oxygen species (ROS) were detected by fluoresent probe method and the levels of adenosine triphosphate (ATP) were detected by luciferase method.Cell viability was evaluated by using cell count Kit-8.Peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A(TFAM) and phospho-adenosine monophosphate activated protein kinase(p-AMPK) protein expression were detected by using Western blotting. Results (1)Compared with the control group, the mRNA expressions of TNF-α and IL-1β(2.548±0.154 vs.1.000±0.001, P=0.000; 2.912±0.102 vs.1.000±0.001, P=0.000), the levels of ROS[(245.307±13.379)RFU vs.(69.460±7.257)RFU, P=0.000] and ATP[(1.558±0.008) nmol/mg protein vs.(1.016±0.025) nmol/mg protein, P=0.000] significantly elevated, and the cell viability(0.840±0.013 vs.1.000±0.001, P=0.000)decreased, while the protein expression of NRF-1(0.406±0.045 vs.0.157±0.016, P=0.017), TFAM(0.605±0.025 vs.0.416±0.013, P=0.005)elevated in LPS+ IFN-γ group, and the differences were significant(all P<0.05). (2)Compared with LPS+ IFN-γ group, the levels of ATP [(1.763±0.028) nmol/mg protein vs.(1.558±0.008) nmol/mg protein, P=0.000], the cell viability(0.910±0.024 vs.0.840±0.013, P=0.008) were elevated, while the protein expression of PGC-1α(0.724±0.027 vs.0.586±0.039, P=0.000), NRF-1(1.036±0.211 vs.0.406±0.045, P=0.000), TFAM(0.786±0.058 vs.0.605±0.025, P=0.002) and p-AMPK(1.094±0.223 vs.0.755±0.084, P=0.014) were elevated in IL-6 group, and the differences were significant(all P<0.05). (3)Compared with IL-6 group, ATP[(1.187±0.005) nmol/mg protein vs.(1.763±0.028) nmol/mg protein, P=0.000]and the cell viability(0.680±0.040 vs.0.910±0.024, P=0.000) all decreased in siRNA group, while the protein expression of PGC-1α(0.631±0.022 vs.0.724±0.027, P=0.020), NRF-1(0.386±0.066 vs.1.036±0.211, P=0.000), TFAM(0.593±0.022 vs.0.786±0.058, P=0.009) and p-AMPK(0.365±0.063 vs.1.094±0.223, P=0.002) significantly decreased in siRNA group, and the differences were significant(all P<0.05). Conclusions IL-6 can increase mitochondrial biogenesis in activated AS, which is probably mediated through up-regulating the expression of AMPK. Key words: Activated astrocyte; Interleukin-6; Mitochondrial biogenesis; Adenosine activated protein kinase