Abstract: The present study was set out to explore the antioxidant effect of methanolic leaf extract of Ficus hispida Linn. (FH) against azathioprine (AZA) induced liver injury in male Wistar rats. In vitro antioxidant activity of FH was examined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical inhibition assays, the extract exhibited IC50 values of 29.33 ±1.14 and 21.51 ±0.96 μg mL-1, respectively. The in vivo experiments revealed that AZA (50 mg kg-1 body weight; single intraperitoneal injection) caused a severe oxidative insult in the liver, which was depicted by a substantial drop in the enzymic [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)] and non-enzymic antioxidants [glutathione (GSH), Vitamin C (Vit C), Vitamin E (Vit E)]. In contrary, pretreatment with FH (400 mg kg-1 body weight; pretreated orally for 21 days) maintained the antioxidant status at near normalcy. In addition, AZA induced lipid peroxidation (LPO) was also significantly alleviated by FH administration. These results underscore that Ficus hispida leaves possess remarkable antioxidant potential and hence it could be evaluated as an effective supplement to attenuate azathioprine induced oxidative stress.