Objective A PCR array was used to explore the effects of pyroptosis on extensor digitorum longus(EDL) loss in aging rats after a 32 weeks weight-bearing running regime. Methods Ninety SD rats were randomly divided into three groups: control group (C0 group, n= 10), aging no exercise group (C group, n= 40), and aging weightbearing running group (R group, n= 40). After 8, 16, 24, and 32 weeks of intervention, the C and R groups were divided into C8 group, C16 group, C24 group, C32 group, R8 group, R16 group, R24 group, R32 group (n= 10). After the intervention, the body weight, lean body mass, and EDL wet weight were measured. HE staining was used to observe the shape of muscle fibers, and the fiber cross-sectional area (FCSA) was calculated. The expression of key pyroptosis proteins, NF-κB, ASC, GSDMD, and Caspase1, were tested by Western Blot. Differentially expressed genes of pyroptosis of EDL were screened by PCR array, and the accuracy of the array result were verified by qPCR. Results (1) Body weight continued to increase in the C group, while that in R group was relatively stable. The lean body mass and its percentages were significantly lower in the C32 group than the C0 group. The lean body mass percentages were significantly higher in the R8, R24, and R32 groups than their corresponding C groups (P< 0. 05). (2) EDL wet weight and FCSA were significantly higher in the R24 and R32 groups than the C24 and C32 groups. The FCSA of each C group was lower than that of the C0 group (P< 0. 05). (3) The contents of NF-κB and GSDMD in the C16 and C24 groups; that of ASC in the R16 group; and that of Caspase1 in the C8, C16, C24, and R8 groups were significantly higher than those in the N group (P< 0. 05). The contents of NF-κB in the R16 and R24 groups, ASC and GSDMD in the R16 group, and Caspase1 in R group were lower than those in the respective C groups (P< 0. 05). (4) The PCR array showed that the expression of pyroptosis genes gradually decreased in the R group with training time. The downregulation of Naip6 and the key pyroptosis gene Casp1 in the R16/ C16 and R32/ C32 groups was verified by qPCR and was consistent with the array result. Conclusions 32 weeks of weight-bearing running alleviated muscle loss in aging rats by inhibiting pyroptosis.