Objective To observe the protein expressions of PI3Kp110, pAkt, pGSK3β of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) signaling pathway in the whole blood of patients with Kashin-Beck disease and analyze the status of PI3K/Akt signaling pathway. Methods Patients with Kashin-Beck disease ( KBD group ) were from six counties ( Xunyi , Linyou , Yongshou , Qianyang , Changwu and Long County) of Shannxi Province in Kashin-Beck disease areas , and the healthy controls (control group) were matched by age and sex. Venous blood was collected from patients and healthy controls. Trizol method was applied to extract the whole blood protein; protein expression levels of PI3K/Akt signaling pathway in whole blood were detected by Western blotting; the gray values were observed and recorded by the sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and GDS-8000 gel imaging analysis system. Differences between the two groups were assessed by Student’s t-test. Results Compared age and sex between KBD group and control group, differences were not statistically significant(t=0.701, P>0.05;χ2=0.400, P>0.05). The protein expression levels of PI3Kp110, pAkt and p-GSK3β in KBD group were higher than that in control group(156.1 ± 92.1 vs. 79.5 ± 21.5, 113.7 ± 15.2 vs. 43.3 ± 10.7 and 105.9 ± 17.5 vs. 37.3 ± 12.0, respectively) and the differences were statistically significant (t=2.563, 6.567, 7.916; all P < 0.05 or < 0.01). Conclusion The PI3Kp110, pAkt and p-GSK3β expressions of signaling pathway proteins in the whole blood of patiens with Kashin-Beck disease are up-regulated significantly and the status of PI3K/Akt signaling pathway is activated.