Objective: This study of rabbits with ovalbumin-induced arthritis (OIA), a model of rheumatoid arthritis (RA), examined the time course of changes in synovial neovascularization based on imaging from power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS).Methods: 25 male New Zealand rabbits were in the OIA group and 5 were in the control group. Both rear knee joints of all rabbits were examined using conventional US and CEUS over 16 weeks. The knee synovia of OIA rabbits were sampled by US-guided biopsy, and the expression of CD31 and VEGF were determined by immunohistochemistry. The correlation of microvessel density (CD31 positivity) and VEGF at different times was analyzed using multimodal US.Results: OIA rabbits had increased synovial expression of CD31 and VEGF from week 6 to 12 (P<0.01). During the early stage of CEUS enhancement, dot enhancement was more common on weeks 6 and 8, and strip enhancement was more common on weeks 12 and 16 (P<0.05). There were significant positive correlations of synovial CD31 and VEGF expression with PDI grade, CEUS grade, and peak intensity (PI) (P<0.05 for all).Conclusions: OIA rabbits mimicked early-stage RA at 4 to 8 weeks, middle-stage RA at 8 to 12 weeks, and late-stage RA at 12 to 16 weeks. PDI, CEUS, and PI, especially when combined with CD31 expression, accurately characterized the extent of synovial vascularization. Increased vascular morphology based on CEUS may have value for the early diagnosis of RA.