Objective To investigate the effect of Wnt/β-catenin signal pathway on the apoptosis in steroid-induced avascular necrosis of femoral head (SANFH) in rats. Methods Seventy-two male Sprague Dawley rats (weighing, 200-230 g) were randomly divided into the control group (group A, n=24), the model group (group B, n=24), and the intervening group (group C, n=24). The rats in groups B and C were injected with lipopolysaccharide and methylprednisolone (MPS) to establish the SANFH model. The rats in group C were injected intramuscularly with human recombinant secreted frizzled related protein 1 (SFRP1) [1 μg/(kg·d)] at the first time of MPS administration for 30 days. The rats in group A received saline injection at the same injection time of group B. The general condition of rats in groups B and C was observed during modeling and after modeling. At 2, 4, and 8 weeks after last injection of MPS, 8?rats were sacrificed to harvest the femoral head. Histological staining was performed to evaluate osteonecrosis. Apoptosis was detected via TUNEL staining. The expressions of Wnt/β-cate nin pathway signaling molecules (activated β-catenin and c-Myc) were detected by immunohistochemistry and Western blot. Results Six rats were added in groups B and C because of 6 deaths. The other rats survived to the end of experiment. Normal bone structure was observed in group A; osteonecrosis of bone structure disturbance and disruption of the trabecula were found with time in groups B and C. Group C had the highest empty lacuna rate and apoptosis rate, followed by groups B and A, showing significant difference between groups (P < 0.05). The expression levels of activated β-catenin and c-Myc were significantly lower in group C than groups A and B (P < 0.05), and in group B than group A (P < 0.05). Conclusion Wnt/β-catenin signal pathway is involved in the pathogenesis in early SANFH model and its?possible mechanism?is to affect the cell cycle and cell apoptosis by the regulation of c-Myc expression.