Objective To observe the mRNA and protein expression of wingless-type MMTV integration site family member 5a (Wnt5a), glycogen synthase kinase 3 (GSK3), and β-catenin, as well as the muscle fibers and adipose tissue presented in pathological staining in the gastrocnemius muscle of white rabbits with blunt gastrocnemius contusion injuries, and provide a basis for revealing the repair mechanism of the pressing and kneading method in treating skeletal muscle injury. Methods Forty-two healthy male and female New Zealand white rabbits were selected. They were randomly divided into blank group, model 3-day group, model 7-day group, model 14-day group, press-and-knead 3-day group, press-and-knead 7-day group, and press-and-knead 14-day group, by using a random number table method, with 6 rabbits in each group. Samples of the model groups and the press-and-knead groups were taken on the 4th, 8th and 15th days after operation. The mRNA and protein expression of Wnt5a, GSK3, and β-catenin were detected by quantitative polymerase chain reaction and Western blot; the muscle tissue myofibers and adipose tissue were observed by hematoxylin and eosin (HE) staining and oil red O staining. Results The HE staining results showed that significant fibrous tissue proliferation and inflammatory cell infiltration occurred in the model 7-day group; in the model 14-day group, some muscle fibers were degenerated, necrotic, and regenerated, accompanied by fibrous tissue proliferation, slight inflammatory cell infiltration, and slight calcification; in the press-and-knead groups, obvious muscle fiber degeneration, necrosis, and regeneration, and inflammatory cell infiltration were observed, accompanied by significant fibrous tissue proliferation. The oil red O staining results showed that adipocyte deposition was visible in the model groups, which was the heaviest in the model 7-day group; in the press-and-knead groups, muscle fibers and sequences were not significantly damaged, and a small amount of adipocyte infiltration was visible in the interstitial space. There were statistically significant differences in the mRNA expression and protein expression of Wnt5a, GSK3, and β-catenin in the gastrocnemius among groups (P<0.001). Conclusions The histopathological changes of gastrocnemius muscle injury recover gradually over time, and the pressing and kneading method stimulates the mRNA expression activities of Wnt5a, GSK3, and β-catenin, which may slow down the degradation of β-catenin protein by the scaffolding protein complex (of which GSK3 is an important component), so that the protein level of β-catenin is maintained in the stable range at all times. This leads to a reduction of fatty degeneration in the gastrocnemius muscle after the intervention of pressing and kneading method, and promotes the functional repair of the injured skeletal muscle.