OBJECTIVE To determine whether morroniside, a compound in Cornus officinalis Sieb et Zucc can prevent cultured human umbilical vein endothelial cells (HUVEC) from damage by high ambient glucose. METHODS HUVEC was incubated in glucose, 5 or 30 mmol/L, either alone or in the presence of morroniside (final concentration 100, 10, and 1 micromol/L, respectively) for 48 h. The proliferation of HUVEC was quantified by MTT method; its cycle was analyzed by flow cytometry; morphological change was observed with fluorescence microscopy. RESULTS Survival of HUVEC cultured in high ambient glucose was significantly decreased when compared to that in normal concentration of glucose (P<0.01). High ambient glucose also lowered the rate of cells entering into S-phase, along with severe morphological damage. With the intervention of morroniside (final concentration 100 and 10 micromol/L), the cell survival was significantly recovered (P<0.01, P<0.05, respectively), accompanied with increased S-phase rate and less extent of morphological damage. CONCLUSIONS Morroniside protected HUVEC against high ambient glucose induced injury, which suggested that morroniside could exert a beneficial effect on preventing diabetic angiopathies.