OBJECTIVE: To study the protective effects of soluble ornithine cyclase activator cinaciguat (called CIN for short) on human umbilical vein endothelial cells (HUVECs) under the condition of high glucose. METHODS: HUVECs were treated with glucose 33.3 mmol/L to induce oxidative stress injury model. HUVECs were divided into normal group, high glucose group and high glucose+CIN 0.01, 0.1, 1 and 10 μmol/L groups. The cell viability was detected by MTT assay, and the survival rate of cells was callulated. Besides, HUVECs were divided into normal group, normal+CIN 1 μmol/L group, high glucose group, high glucose+CIN 1 μmol/L group. MDA content and SOD activity were determined by TBA method and xanthine oxidase method; mRNA expression of ICAM-1 and VCAM-1 were determined by RT-PCR. RESULTS: Compared with normal group, survival rate decreased in high glucose group (P<0.05); compared with high glucose group, that increased in high glucose+CIN 0.01, 0.1, 1 and 10 μmol/L groups, in concentration-dependent manner; there was no statistical significance in survival rate between high glucose+CIN 1 μmol/L group and high glucose+CIN 10 μmol/L group (P>0.05). Compared with normal group, MDA content and mRNA expression of ICAM-1 and VCAM-1 increased in high glucose group, while SOD activity decreased (P<0.05); above indicators had no significant change in normal+CIN 1 μmol/L group (P>0.05). Compared with high glucose group, MDA content and mRNA expression of ICAM-1 and VCAM-1 decreased in high glucose+CIN 1 μmol/L group, while SOD activity increased (P<0.05) . CONCLUSIONS: CIN can protect high glucose-induced HUVECs injury in vitro. The mechanism may be associated with inhibition of oxidative stress and inflammatory response.