Tramadol is used worldwide and is listed in many medical guidelines to treat both acute and chronic pain. There is growing evidence of abuse of tramadol in some African and West Asian countries. Tramadol has some side effects. The present study was designed a follow-up and treatment of the cell biological, histochemical and Pathological response which might be induced in the ileum of tramadol application. A total number of 70 adult males Swiss albino mice were obtained and survived during experiments from/in (Autoradiographic lab. of Cell Biology and Immunology studies, Faculty of Science, South Valley University), under supervision Dr. Abdel-baset Aref Mohamed. At the time of the experiments, the mice were aged 90 ± 5 days and weighed 30 ± 2 g. All male mice were kept under the same conditions of light-dark cycle (12h-12h), temperature (23 ± 2^oc), and humidity (37-40%). They were supplied standard food and water ad libitum. The daily injections of tramadol for 20 reach to 40 days highly changed the volume of nuclei and protein, RNA and DNA materials contained in the cells lining ileum, therefore, extensively and severely destructions showed in the normal histological architecture of ileum of male mice.  
Finally, we could say, Although, tramadol has many cytological, histochemical and histopathological, side effects on ileum of male mice but the treatments with Lagenaria siceraria and melatonin have a more effective therapeutic effect on tramadol side effects.