This study was designed to evaluate the effects of the combined treatment with an anti-coagulant (enoxaparin) agent and a lipid-lowering agent (lovastatin) on prevention or decrease in the occurrence of steroid-induced osteonecrosis in rabbits. A total of 112 rabbits, which were injected intramuscularly with 20 mg/kg of methylprednisolone acetate were divided into four groups and treated as follows: one group received enoxaparin combined with lovastatin (EL; n = 30), another received enoxaparin alone (EA; n = 28), another received lovastatin alone (LA; n = 28) and the last received no treatment (non-prophylactic; NP, n = 26). Haematological examination for serum lipid levels and prothrombin time was carried out and both femora and humeri were examined histopathologically for the presence of osteonecrosis (ON) before injection and at 2, 4, 8 and 12 weeks after the injection. The incidence of ON in the EL group (15%) was significantly lower than that observed in the NP group (68%). The incidence in the EA and LA groups was also significantly lower than that in the NP group (31%, 35%vs. 68%). The fat cell sizes of the bone marrow in both EL (46.49 +/- 1.27 microm) and LA (50.8 +/- 2.31 microm) groups were lower than in the NP group (59.89 +/- 6.33 microm). The prothrombin time was prolonged and plasma lipid levels were reduced in the EL group during the study. Combination treatment with an anti-coagulant agent and a lipid-lowering agent can reduce the incidence of steroid-induced ON in rabbits. Future evaluation in clinical practice is necessary.