Objective To investigate the effects of intravenous injection of alpha;-crystallin on retinal ganglion cells (RGC) and some important organs of the Long Evans rats. Methods RGC were retrogradelabeled by fluorogold through bilateral superior colliculus and lateral geniculate body for seven days before optic nerve crush injury. Twenty-three Long Evans rats were used for this study, including three rats of normal control group and 20 rats of experimental group. Twenty rats were randomly divided into saline control group and three alpha;-crystallin injection groups, which received tail vein injection of 1.25 ml isotonic saline and three different concentrations (1times;10-2, 1times;10-1 and 1 g/L) of alpha;-crystallin respectively, once every two days and totally seven times. After two weeks, the labeled RGC were counted, and the pathological changes on liver, kidney, brain, spleen and the lungs were investigated. Results Compared with the normal control group, although the number of RGC markedly decreased after two weeks of optic nerve crush injury in every group, the number of RGC in alpha;-crystallin-treated groups was more than those in the saline control group. There were 2074plusmn;150 RGC per mm2 in normal control group, 85plusmn;15 RGC per mm2 in saline control group, 124plusmn;26 RGC per mm2 in 1times;10-2 g/L alpha;-crystallin group, 128plusmn;31 RGC per mm2 in 1times;10-1 g/L alpha;-crystallin group, 164plusmn;20 RGC per mm2 in 1 g/L alpha;-crystallin group (F=18.660, P＜0.01). No congestion, swelling, inflammation and other pathological changes were found in liver, kidney, brain, spleen and lung. Conclusions Intravenous injection of alpha;-crystallin protein has protective effects on RGC after the optic nerve crush injury, and no significant effects on important organs.