Background: Grape seed is a natural herb with many suggested pharmacological effects related to many biologically active compounds in its extract and fractions. Grape seed pharmacological effect is investigated in mice psoriasis like model. Methods: A thirty male albino mice, six weeks’ age used in this research and were divided into five groups. Group I apparently healthy. Group II induction group, imiquimod 5% cream once daily used at the back skin of the animal for five days. Group III, IV and V treatments groups. Group III clobetasol ointment 0.05%, group IV Grape seed extract and group V Grape seed petroleum ether fraction for five days. Results: A high significant increase was found between the apparently healthy and imiquimod induced group for all of the investigated parameters except munro abscess was significant increase. For the grape seed extract group, it was found A significant difference in immunohistochemistry score of IL17, also significant decrease in vascular endothelial growth factor (VEGF) with high significant decrease of other immunohistopathology measurement like parakeratosis. Conclusion: Grape seed extract may have a role in imiquimod-induced psoriasis like skin inflammation in mice treatment which make it a future candidate therapy for psoriasis.