Objective: To observe the uptake of ⁹⁹Tc^m-3 polyethylene glycol Arg-Gly-Asp dimer (3PRGD₂) in rat models of rheumatoid arthritis (RA), in order to provide theoretical foundation for early diagnosis of RA. Methods: The healthy female SD rats were divided into collagen induced arthritis (CIA) group (n=100), osteoarthritis (OA) group (n=20) and control group (n=20). Bovine collagen type Ⅱ emulsion was used for arthritis induction to establish CIA models. OA models were established by injection of L-cysteine and papain. Gamma imaging was performed before and 15 d, 30 d after the model establishment. The mediastinum was selected as non-target (NT) area and the target (T)/NT ratios were calculated. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), α_Vβ₃ before and after the model establishment were measured. Pathological and immunohistochemical detection were performed. One-way analysis of variance, Pearson and Spearman correlation analyses were used to analyze the data. Results: There were 58 CIA models successfully established. Before the model establishment, T/NT ratios of CIA group, OA group and control group were 0.215±0.049, 0.210±0.050, 0.209±0.051, respectively (F=0.093, P>0.05). The T/NT ratios of the above three groups were 0.405±0.230, 0.223±0.045, 0.211±0.049 (F=12.601, P<0.05) 15 d post-model establishment, and those were 0.572±0.182, 0.238±0.045, 0.212±0.055 (F=65.147, P<0.05) 30 d post-model establishment. T/NT ratios of CIA group were positively correlated with the levels of serum VEGF, TNF-α, α_Vβ₃, pathological score and the levels of immunohistochemical markers (VEGF, TNF-α, α_Vβ₃, CD31, CD34; r values: 0.391-0.721, r_s values: 0.365-0.669, all P<0.05). Conclusion ⁹⁹Tc^m-3PRGD₂ can be specifically up-taken by RA lesions in rat models, thus has the potential in early synovial neovascularization imaging of RA.