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Effect of swimming exercise on serotonin (5-hydroxytryptamine, 5-HT) expression and apoptosis in social isolation rats during old age was in-vestigated. Rats in the old social isolation groups were housed alone per cage for 4 weeks. Rats in the swimming exercise groups were al-lowed to swim for 30 min once daily for 4 weeks. Morris water maze task determined spatial working memory and elevated plus maze test determined anxiety. Immunohistochemistry for tryptophan hydroxylase (TPH) and 5-HT in the dorsal raphe and for doublecortin (DCX) in the hippocampal dentate gyrus was conducted. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in the hippocampal dentate gyrus was performed. Western blot analysis for Bax, Bcl-2, and cytochrome c in the hippocampus was conducted. So-cial isolation in rats of old age reduced spatial working memory and in-creased anxiety level. Swimming exercise enhanced spatial working memory and suppressed anxiety level. Social isolation in rats of old age inhibited TPH and 5-HT expression in dorsal rape. Swimming exercise increased TPH and 5-HT expression. Social isolation in rats of old age inhibited DCX-positive cells in the hippocampal dente gyrus. Swimming exercise increased DCX-positive cells. Social isolation in rats of old age increased TUNEL-positive cells, Bax and cytochrome c expression, and decreased Bcl-2 expression, which promoted apoptosis. Swimming ex-ercise suppressed TUNEL-positive cells, Bax and cytochrome c expres-sion, and increased Bcl-2 expression, which inhibited apoptosis. Swim-ming exercise improved 5-HT expression and suppressed apoptosis to alleviate anxiety and memory impairment during old age.