Objective To explore the mechanism of exercise intervention in improving autism-like behaviors in Shank3 gene knockout (Shank3^-/-) induced autism spectrum disorder (ASD) rat models from an autophagy perspective through 8-week swimming intervention.Methods Based on genotype identification and exercise intervention, rats were divided into four groups (n=15): wild-type control group (WC), Shank3^-/- control group (KC), wild-type swimming group (WS), and Shank3^-/- swimming group (KS). KS and WS groups underwent 8 weeks of swimming exercise, 5 d/week, gradually increasing to and maintaining 40 min/session. Behavioral experiments, including self-grooming test, marble burying test, and hole-board test, were conducted 24 h after the final swimming intervention. Tissue sampling was performed 12 h after behavioral testing. Transmission electron microscopy was used to observe autophagosome numbers in the striatum region. Immunofluorescence staining was employed to observe the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and selective autophagy adaptor protein (p62). Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to detect protein and mRNA expression of Beclin1, LC3, p62, autophagy-related protein 5 (Atg5), autophagy-related 16-like protein 1 (Atg16L), and lysosome-associated membrane protein 1 (LAMP1) in striatal.Results Compared with the WC group, rats in the KC group exhibited significantly higher self-grooming frequency and duration (P0.05), increased marble burying behavior (P0.01), and elevated frequencies in both hole-board exploration and single-hole exploration (P0.05). Following 8 weeks of swimming intervention, the KS group demonstrated significantly reduced self-grooming duration, marble burying behavior, and single-hole exploration frequency compared to the KC group. Furthermore, compared to the WC group, the KC group displayed abundant autophagosomes in the striatum region, along with significantly elevated protein and mRNA expression levels of Atg5, Atg16L, p62, and LC3II/LC3I ratio (P0.05), increased Beclin1 protein levels (P0.05), and markedly decreased LAMP1 protein and mRNA expression levels (P0.05). Following the 8-week swimming intervention, the KS group exhibited significantly reduced protein and mRNA expression levels of Atg5, Atg16L, p62, and LC3II/LC3I ratio (P0.05), decreased Beclin1 protein levels (P0.05), and significantly elevated LAMP1 protein and mRNA expression levels (P0.05) compared to the KC group.Conclusion Early 8-week swimming can alleviate stereotyped behaviors in Shank3^-/- rats by regulating striatal cell autophagy.