Population growth, changes in lifestyles, increase in diseases, and natural and unnatural accidents have caused ever increasing importance of the health care chains. On the one hand, the importance of blood as a rare and vital element, and on the other hand, the specific conditions of transportation and maintenance, have been challenging researchers in recent years. The importance of this area will escalate especially in crisis occurrence and severe shortage of blood. In this paper, a mathematical model of a closed-loop blood supply chain under uncertainty is proposed, in which Reverse Logistics and emergency situations are also considered. Due to the complexity in solving the proposed model, after putting forward accurate method to validate the model, a hybrid algorithm based on genetic algorithm(GA) and simulated annealing (SA) is utilized. Then, the validation of this hybrid algorithm is evaluated in comparison with the results of GAMS IDE/Cplex software in solving small, medium and large-sized problems. Finally, the results of the sensitivity analysis are presented.