Objective To explore the effect of prevention and treatment on steroid-induced osteonecrosis of mice femoral head(ONFH) treated with metformin. Methods Thirty-six Kunming mice were randomly divided into three groups (n = 12):A (Control Group), B (Model Group)and C (Prevention Group). For producing ONFH mice models, did the intraperitoneal injection of horse serum (10 mL/kg) to B and C firstly. After two weeks, continuing the intraperitoneal injection of horse serum (5 mL/kg) again with the prednisolone intramuscularly [45 mL/(kg· day), totally for 5 days]. Meanwhile, feeding normal saline 10 mL/(kg·day) to B and feeding metformin hydrochloride [0.2 g/(kg·day)] to C. For A, mice were only given normal saline intramuscularly and intragastrically in equal quantity at the same time. The contents of serum cholesterol (TC), triglycerid (TG), plasma von willebrand factor (VWF) and plasminogen activator inhibitor 1 (PAI-1) were determined at the 2nd, 4th and 6th week after treatment. The micewere sacrificed at 2nd, 4th, and 6th weekafter treatment, and femoral heads were harvested to do histopathology analysis. Results The appearance and shape of the femoral head and the surface of cartilages were normal. The percentage of empty osteocyte lacunae in B was significantly higher than that in C (P < 0.05), there was no significant difference between A and C (P>0.05). TC and TG contents in C were significantly lower than that in B in 2th、4th、6th weeek(P<0.05), and higher than that in A(P<0.05). VWF and PAI-1 level in C were significantly lower than that in B at 2nd and 4th week (P<0.05), but there were no statistical significance at 6th week. there were no statistical significance for the comparison between A and C. Conclusion Metformin can prevent steroid-induced ONFH by improving hyperlipemia, hypercoagulability and hypofibrinolysis, then effectively prevent osteonecrosis.