Background and Aim of Work: Peripheral nerve injuries are frequently confronted in clinical practice due to several reasons such as surgery or accidental trauma. They are often associated with poor nerve regeneration and inadequate functional recovery. Therefore, this study was planned to evaluate and compare the possible effect of erythropoietin (EPO) versus curcumin on crush injury of the sciatic nerve in rat model. Material and Methods: Seventy-eight adult male albino rats were randomly allocated into 5 groups: control sham operated, sciatic nerve injury (SNI), untreated, SNI+EPO and SNI+curcumin. SNI was induced via clamping the right sciatic nerve with a sterile tissue forceps for one minute. After 24hrs, SNI+EPO group was injected intraperitoneally with EPO (5000IU/ kg) daily for two weeks. SNI+curcumin group was given curcumin (40mg/kg) daily orally for two months. The compound muscle action potential (CMAP) amplitudes were recorded at the end of each experimental period. Sciatic nerve specimens were then processed for hematoxylin and eosin, osmic acid stain, toluidine blue stain and immunohistochemical staining for neurofilament (NF). Number and diameter of nerve fibers, ratio of the myelin area to the nerve fiber area as well as area percent and optical density of NF were measured and statistically analyzed. Results: Both EPO and curcumin treated groups exhibited improvement in the histological structure of the sciatic nerve as well as significant increase in CMAP. Also, morphometric measurements including; number and diameter of nerve fibers, ratio of the myelin area to the nerve fiber area as well as area percent and optical density of NF were significantly increased compared to both SNI and untreated groups. However, all measured parameters were significantly higher with EPO as compared to curcumin. Conclusion: EPO promotes structural and functional recovery and enhances regeneration of crushed sciatic nerve better than curcumin.