Objective To explore whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) can improve learning, memory and cognitive decline by regulating autophagy levels in naturally aging rats. Methods Sprague-Dawley rats were reared in a barrier environment to the age of 24 months. Behavioral studies select aging rats with obvious cognitive decline; the rats were divided into a cell transplantation group ( group H) and a normal saline group (group C). For comparison, a normal group ( group N) of 3-month-old rats was included. Rats in group H were injected with 2×10P>6P>> hUCMSCs in a volume of 500 μL through the tail vein. Rats in groups C and N were injected with an equal volume of sterile saline through the tail vein. Injections were performed once per week for 4 weeks. Changes in learning and memory ability were assessed using the Morris water maze, Y maze, and novel object recognition test. Changes in rat hippocampal neuron morphology were assessed using hematoxylin-eosin staining. Relative expression levels of hippocampal LC3II/ I, Beclin1, and p62 were assessed using Western Blot. Results Behavioral analyses showed that the learning and memory abilities were significantly better in groups H and N than in group C. HE staining of nerve cells in the CA1 and DG areas of the hippocampus revealed more regular arrangements, more complete cell structure, and more intact nuclei in groups H and N. Conversely, the number of neurons in the CA1 area was reduced, cell arrangement was loose, nuclei were shrunken, and degenerative disease was present in group C. p62 protein content was significantly lower in groups H and N than in group C, while Beclin1 and LC3II/ I protein levels were significantly higher in groups H and N than in group C. Conclusions Intravenous injection of hUCMSCs improved learning, memory, and cognitive decline in naturally aging rats, presumably by restoration of autophagy.