Background/Aim: Considering the modulatory role of medial septum (MS) on behavioral and autonomic activities, and its neural connections with other brain areas having effects on the immune system, the role of MS on some immune responses has been investigated. Methods: Hyperreactivity scores, total count and differential count of WBC, phagocytic activity of blood WBC, leukocyte adhesive inhibition index (LAI), delayed type of hypersensitive (DTH) reaction and serum corticosterone (CORT) concentration were measured in MS-lesioned, sham-operated and control rats after 2 and 3 weeks of operation. The results of MS-lesioned rats were compared to those in the control and sham-operated rats. Results: The hyperreactivity score was not changed in the MS-lesioned rats. The phagocytic activity of blood WBC was increased but the DTH reaction and percentage of LAI were decreased in the MS-lesioned rats compared to the control and sham-operated rats 2 weeks after surgery. The serum CORT concentration was increased in the MS-lesioned rats compared to the control and sham-operated rats 2 weeks after surgery. After 3 weeks of MS lesion these immunological parameters and CORT concentration returned back to the normal values indicating a transient change of these parameters. Conclusion: This study concludes a complex and differential regulatory role of MS in the immune functions which are not linked with the hyperreactive behavior in rats. This immunoregulation of MS appears to be different from that of the lateral septum like their dissimilar modulatory roles in some behaviors.