The aim of this study was to evaluate the ability of power Doppler sonography (PDS) with ultrasound contrast agent to assess the synovial perfusion changes induced by intra-articular steroid injection therapy in the knee joints of patients with rheumatoid arthritis (RA). Eighteen RA patients (16 women, 2 men) with a history and signs of active knee synovitis were studied. Tenderness was evaluated using Thompson’s modified index of synovitis activity. All patients underwent joint aspiration followed by intra-articular injection of 40 mg of triamcinolone hexacetonide. Gray-scale ultrasonography and PDS with an intravenous ultrasound contrast agent (Levovist) examinations were carried out before and 3 weeks after the intra-articular steroid injection. The calculation of the time–intensity curves provided a quantitative estimation of the synovial perfusion. The median values of the index of synovitis activity decreased significantly from 7.0 (95% confidence interval (CI) 6.0–8.0) to 3.0 (95% CI 2.0–4.0) (p<0.01) 3 weeks after the intra-articular steroid injection. All patients showed a reduction of PDS signal after intra-articular steroid therapy and the baseline and follow up median values of the area underlying time–intensity curves were 7.48 (95% CI 5.79–8.73) and 2.45 (95% CI 1.92–3.61), respectively. The comparison between baseline and follow-up median values of the area under the curves showed a statistically significant reduction of PDS findings (p<0.01). At follow-up examinations the changes in the index score of the synovitis activity were significantly correlated to the changes in the values of the area underlying time–intensity curves (r=0.785; p<0.01). A significant correlation was also observed between baseline values of the area underlying time–intensity curves and C-reactive protein (CRP) (r=0.548; p=0.023). In conclusion, PDS with an intravenous ultrasound contrast agent has been shown to be able to detect changes in synovial perfusion after intra-articular steroid injection and may be an additional useful method in the evaluation of synovial inflammation and in the assessment of the therapeutic response.