Using the rat model of type 2 diabetes and the methods of Tunnel dyeing and Western blot,this study aimed to investigate effects of aerobic exercise plus spirulina supplement(SP) on learning and memory function,ERK/CREB signaling pathway and cleaved caspase-3 expression in hippocampus of type 2 diabetes rats. The model rats were randomly divided into diabetes model group(DM),diabetes exercise group(DE),diabetes SP group(DS)and diabetes exercise SP group(DES),additionally provided control group(C) without any intervention(10 rats each group). Learning and memory and the hippocampus cells apoptosis rates were observed. The expressions of p-ERK,p-CREB,ERK,CREB and cleaved caspase-3 were tested;at the same time,changes of blood glucose and serum insulin,and so on were examined in the end of the experiment. Results:Compared with group DM,blood glucose and serum insulin levels of the intervention groups decreased significantly(P<0.05 or P<0.01),the escape latencies of the groups were shortened and the numbers plateau crossing increased(P<0.05 or P<0.01). The cells apoptosis rate and cleaved caspase-3 expression of the rats decreased significantly(P<0.05 or P<0.01),the levels of P-ERK/ERK,P-CREB/CREB in the groups increased obviously(P<0.01). The improvement of the above indicators was more obvious in group DES than that in group DE and DS. These results suggested that aerobic exercise and SP could reduce blood glucose and improve learning and memory of type 2 diabetes rats,and the neuroprotective effect of exercise combined with SP was better than those in exercise and SP alone. The mechanism is related to the up-regulation of ERK/CREB signaling pathway,and down-regulation of cleaved caspase-3 expression then further inhibit hippocampus cell apoptosis for type 2 diabetes rats.