2Cl-C.OXT-A (COA-Cl) is a novel synthesized nucleoside analogue with the molecular weight of 284. It is soluble, stable and easy to synthesize. It has been reported that COA-Cl enhances angiogenesis in human umbilical endothelial cells (HUVEC). The previous study in our lab showed the neuroprotective effects of COA-Cl on ischemia stroke by reducing infarct volume and attenuating the behavioral deficits. The purpose of the present study is to evaluate the neuroprotective effect of COA-Cl on intracerebral hemorrhage (ICH), another common type of stroke, and investigate the potential mechanism of action. Sprague-Dawley (SD) rats were used for this study. ICH models were performed by the injection of 100μl autologous blood into the right basal ganglia. COA-Cl (30μg/kg) was injected intracerebroventricularly 10min after ICH. A battery of behavioral tests, including body swing test, forelimb placing test and corner turn test was performed to examine sensorimotor deficits with a time course as 1d, 3d, 5d and 7d after ICH. To understand the potential mechanism of how COA-Cl work at the acute phase of ICH, we examined brain edema 1day after ICH using water content test, and evaluated the anti-apoptosis role of COA-Cl by TUNEL assay. Oxidative stress, a primary cause for the edema formation, was also examined by a DNA oxidative marker (8-OHdG). Our results showed that the rats in COA-Cl group significantly attenuates the sensorimotor deficits and reduces brain edema compared with ICH ones. By immunohistochemistry method, we found that both TUNEL positive cells and 8-OHdG positive cells were fewer around the hematoma of COA-Cl treated rats compared with ICH ones. Theses results indicated that COA-Cl may have neuroprotective effects on ICH that it reduces brain edema, inhibits neuronal loss and improves ICH-induced behavioral deficits. Furthermore, we provide the first evidence that COA-Cl may have an anti-oxidative role, which may be one of the potential mechanisms for its neuroprotective effects.