To investigate the regulatoryeffect of non-denatured type-I collagen (NDC-I) on the immune function inimmunocompromised rats, the immunocompromised model was established by intraperitoneal injection of cyclophosphamide in animal experiments. The thymus index,spleen index, white blood cell countand classification, IgA (immunoglobulin A) level, IgG (immunoglobulin G) level, IL-2 (interleukin-2) level, IL-4 (interleukin-4) level, IL-10 (interleukin-10) level, IFN-γ (interferon-gamma) level, TNF-α (tumor necrosis factor-α) level, activity of lactate dehydrogenase (LDH) in spleen and thymus, as well as histomorphological changes of spleen and thymus, were examined. The results showed compared with the model group, a 30-day NDC-I intervention led to significant increases inthe thymus index (p<0.05) and white blood cell count (p<0.01) of the NDC-I treated group, causingsignificant increases (p<0.01) in their levels of serum IgA, IgG, IL-2, IL-4, IL-10, IFN-γ and TNF-α (as 43.32 µg/mL, 283.32 µg/mL, 1827.17 ng/L, 135.97 pg/mL, 113.87 ng/L, 2302.44 pg/mL and 469.91 ng/L, respectively), and the activity of LDH in spleen. In addition, the histopathological damages of the spleen and thymus werereduced. The obtained results revealed that the NDC-I treatment showed a regulatory effect on the immune function of cyclophosphamide-induced immunocompromised rats. This research also provides a reference for the comprehensive development and full utilization of collagen and other related functional products.