Objective To study the differences of symptoms and pathological features of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis. Methods Wistar and Lewis rats were injected with intermixture of bovine TypeⅡ collage and complete Freund’s adjuvant(CFA) for first immunization, then strengthen it after 14 days and observed the incidence of Wistar-RA group and Lewis-RA group. The degree of paws swelling and the titer of serum anti CII antibody were determined. The pathological changes in toe and joint tissues were examined at 12 weeks, and the expressions of VEGF, IL-6, IL-10 and IL-17A in the synovial membrane of ankle joint were detected. Results After collagen induction, the Wistar and Lewis rats showed paw swelling after 10 d and 14 d, and peaked at 21 d and 24 d, the titer of serum anti CII antibody was significantly increased at third week ( P < 0.01), and arthritis index (AI) was also significantly increased ( P < 0.01). In the Wistar-RA rat group, the rate of molding was 80%, and at fifth weeks, the swelling of the paws subsided and went into a flat level. The molding rate of the Lewis-RA group was 100%, at the seventh week, the swelling of paws subsided and went into a flat level. At 12 weeks, the two model groups showed severe articular cartilage erosion, synovial hyperplasia and inflammatory cell infiltration, neovascularization and pannus formation in the joint synovium, and the bone mineral density of the femur and tibia of the hind limbs was significantly decreased ( P < 0.01). The expression of VEGF, IL-6 and IL-17A in synovium was significantly increased ( P < 0.05, P < 0.01). The expression of IL-10 was obviously decreased ( P < 0.01). Compared with the Wistar-RA group, the paw volume and paw thickness were increased for a longer time in the Lewis-RA group, AI was higher than that of the Wistar-RA group, synovial angiogenesis and pannus formation were more distinct, the expression of VEGF in synovium was significantly higher than that of Wistar-RA group ( P < 0.05), while the expression of IL-17A was significantly lower than that in the Wistar-RA group ( P < 0.05). Conclusions Both the Wistar-RA rat model and Lewis-RA rat model show joint swelling, deformation and decreased activity. AI is increased, the expression of VEGF, IL-6 and IL-17A increased, and the expression of IL-10 decreased, which are consistent with the clinical manifestation. The Wistar-RA rat model has a short duration of swelling, while the Lewis-RA rat model has a longer swelling duration and more severe joint damages. The neovascularization and pannus formation are more obvious. The expression of IL-17A in the Wistar-RA rat model is higher, while the Lewis-RA model has a highly expressed VEGF, which may be related to its pathological characteristics.