Background: Methimazole (MMZ), has been the drug of choice in treatment of human hyperthyroidism for several decades, however its administration may result in unfavorable effects. The spleen can reflect this drug induced immune-toxicity. Nigella sativa oil (NSO) has potent immune-protective action. Aim: The current study aimed to determine the alternation in the structure of the spleen and hematological parameters as a result of MMZ administration and if NSO has protective role in such case. Material and methods: The study was conducted on twenty five adult male albino rats, divided into five groups (n=5), group I served as control, group II received 0.25ml/kg/day of NSO started two weeks before the experiment and continue till its end (for 6 weeks), group III subjected to surgical thyroidectomy, group IV rats treated with MMZ (20 mg/kg/day) and group V pretreated with NSO for 2 weeks and then accompanied with MMZ for 4 weeks in the same dose of group III and IV respectively. At the end of the experiment, spleen specimens were taken and processed for H&E and immunohistochemical stains (CD4and Ki67) in addition to hematological analysis. Results: Remarkable alternations in the structure of the spleen were noticed in rats treated with MMZ. Moreover, RBCs and WBCs counts were reduced in MMZ- treated group. NSO co- administration with MMZ revealed partial improvement in histological structure of the spleen and blood picture. Conclusion: MMZ drug has an obvious immuntoxic effect on the spleen and NSO has relevant protective action.