BACKGROUND The aims of this preliminary study were to evaluate contrast-enhanced ultrasound (CEUS) imaging and the therapeutic response of enlarged superficial lymph nodes in patients with lymphoma before and after chemotherapy and to determine the most useful CEUS response parameters. MATERIAL AND METHODS Forty-three patients with lymphoma, with 43 enlarged superficial lymph nodes, underwent CEUS and conventional ultrasound (US), before treatment and after the first three cycles of chemotherapy. Clinical responses included overall response (OR) and no response (NR). Imaging parameters by time-intensity curve (TIC) included basic intensity (B), wash-out slope and/or decent slope (K), wash-in slope or rise slope (C), time to peak (TTP), area under the gamma curve (Area), arrive time(ATM), peak intensity (PI), change of peak intensity (I) were compared. And receiver operating characteristic (ROC) curve analysis was operated. RESULTS Quantitative parameters of CEUS before and after the first three cycles of chemotherapy showed a significant difference in the AreaΔ, PID, and IΔ in the OR group compared with NR group (P<0.05). There was a significant difference in the Cpre, Areain, PIin, Iin, AreaΔ, PIΔ, and IΔ in the OR group compared with NR group (P<0.05). The effectiveness of the therapeutic response was predicted by the CEUS parameters of IΔ (P<0.05). And ΔArea has the highest diagnostic performance of ineffectiveness. CONCLUSIONS The findings of this study have shown that quantitative analysis by CEUS may be a useful, and objective, imaging method for the evaluation of the therapeutic response of enlarged superficial lymph nodes in lymphoma before and after chemotherapy.