Exposure to formaldehyde (FA) can occurs either in the environment or in workplaces due to its common use in laboratory, industry, household and cosmotic products. This study was carried out to assess toxic effects of subacute exposure to FA on immune system in adult male albino rats and possible relationship to its risk of carcinogenesis. Methods: Fifty adult male albino rats were used for 28 days as follow: Group I: (20 rats) subdivided equally into group Ia negative control and group Ib positive control, Formaldehyde group: (30 rats) divided equally into groups II, III & IV received FA by oral gavage at doses of 20, 40 and 80 mg/kg respectively. At the end of the study, spleen of each rat was dissected and subjected to histopathological examination, immunohistochemical staining for CD4+ and comet assay. Blood samples were withdrawn and used for evaluation of T-lymphocytes subsets (CD3+, CD4+ and CD8+), CD19+ B-lymphocytes and CD56+ natural killer (NK) cells by flow cytometric analysis and cytokines profiles of interleukin 10 (IL-10) & interferon-gamma (IFN-γ) by enzyme-linked immunosorbent assay (ELISA) technique. Results: Histopathological and immunohistochemical studies showed decrease in the size and cellular components of lymphocytes follicles with congestion of sinusoids and decreased expression for CD4+ in FA treated rats. Comet assay detected DNA damage in splenocytes of FA group. There were significant decreases in all T-lymphocytes subsets in groups III &IV with no significant difference was detected in group II. B- lymphocytes showed a significant increase in groups III & IV, however NK cells revealed a significant decrease in group IV. Assessment of cytokines detected a significant increase in IL-10 in all FA-treated rats, while IFN-γ was decreased in groups III & IV. Conclusion: Formaldehyde exposure resulted in dose-dependent immunotoxic effects which may be related to its risk of carcinogenesis.