Tramadol is a utilized medication globally that is included in numerous medical guidelines for the treatment of both short-term and long-term pain. There is an increasing body of research indicating the prevalence of tramadol abuse in certain Middle East nations. Tramadol exhibits certain adverse effects.
              The purpose of the present investigation is examination and treatment of the histopathological reaction that may develop in the spleen following tramadol administration.
               The mice were treated via a dose of tramadol by daily injection for 20 days and 40 days. Additionally, groups of mice were administered tramadol for 40 days, followed by daily treatment with either distilled water, Lagenaria siceraria (L.), or melatonin (MT) for another 40 days.The administration of tramadol significantly impacted the quantity of collagen materials present in the spleen cells. As a result, modifications were observed in the typical histological structure of the spleen.Ultimately, we propose that while tramadol has various adverse effects on the spleen tissues of male mice, the use of L. and MT treatments exhibits therapeutic benefits in alleviating these tramadol-induced side effects.