The aim of this study was to assess the influence of long-term administration of cyclosporine (CsA) on rat intestinal intraepithelial lymphocytes (IEL). Ten male Lewis rats were randomly assigned to either a treatment or a control group. For 12 weeks the treatment group received CsA (5 mg/kg per day) while the control group received the same volume of vehicle. Peripheral blood lymphocytes were counted and IEL were isolated for flow cytometric analysis. Peripheral blood lymphocytes numbers were significantly decreased in the CsA compared with the control group (4.80 +/- 1.02 x 10(6)/mL and 3.34 +/- 0.70 x 10(6)/mL, respectively, P = .029). IEL numbers were increased significantly in CsA compared with the control group. (23.2 +/- 8.0 x 10(6) and 7.8 +/- 1.8 x 10(6), respectively, P = .012). There were no significant differences between the two groups considering IEL phenotypes. In conclusion, CsA did not influence the subpopulation but significantly increased the number of IEL.