Background and Aim of work: Stress and its related comorbid diseases are responsible for many liver pathologies. Nestin, a protein detected in a wide range of progenitor cells, was implicated in hepatic remodeling.  Moreover,  vascular endothelial growth  factor (VEGF) is involved in vessel repair. The aim of this study was to evaluate the effect of chronic restrain stress (CRS) on expression of hepatic VEGF and Nestin. Materials and methods: Twelve male rats were divided into two groups; negative control and CRS. Animals of CRS were restrained individually in ventilated glass tube restrainers daily for 6 hours/day for 3 weeks. The liver samples were stained by hematoxylin and eosin, Masson trichrome and immunohistochemical staining for Nestin and VEGF with morphometric analysis. Results: Exposure to chronic restraint stress for 3 weeks caused hepatic inflammation, deposition  of collagen.   Immunohistochemical   staining   showed   a  coinciding significantly higher positive reaction for VEGF and Nestin in the CRS group. Conclusion: Vascular endothelial growth factor and Nestin immunohistochemical staining were both increased in chronic restraint-induced hepatic stress coinciding with the induced increase in hepatic inflammation, deposition of collagen. Nestin & VEGF