The aim of this experimental study was to examine the effect of Caffeic acid phenethyl ester (CAPE) on steroid-induced osteonecrosis of femoral head (ONFH) in rats. Thirty-one male Wistar albino rats were divided into 4 groups: control group (7 rats), methylprednisolone treatment group (MPS, 8 rats), CAPE treatment group (8 rats) and MPS+CAPE administered group (8 rats). The rats of group MPS and CAPE+MPS, On days 2, 3 and 4 were treated with 20 mg/kg/day methylprednisolone (MPS; Pfizer Pharmaceutical, Puurs, Belgium) intramuscularly. 10 mu mol/kg/day CAPE was intraperitoneally injected to the rats of group CAPE from 13 weeks of age for 4 weeks. The control group was fed and housed under identical conditions without any treatment. All rats were sacrificed at 17 weeks of age by taking blood from the heart. Both proximal femoral parts were taken for histopathological and immunohistochemical analysis . Total oxidant status, total antioxidant status, and oxidative stress index (OSI), lipid parameters, coagulation parameters were assessed in blood specimens. Much lesser amount of osteonecrosis lesions were observed in the MPS+CAPE group compared to MPS group. In immunhisochemical analysis, oxidative stress was found significantly decreased in CAPE+MPS group compared to MPS group. OSI levels were significantly decreased in CAPE+MPS group compared to MPS group (p<0.001). In CAPE+MPS group lipid and coagulation parameters were found positively affected compared to MPS group. In conclusion, CAPE has strong protective effect against the steroid induced femoral head osteonecrosis in rats.