Objective: To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods: Twenty-four SD rats were randomly divided into a control group, a model group and an acupuncture group. Fasting plasma glucose (FPG), fasting insulin (FINS), insulin sensitivity index (ISI), C peptide (C-P), as well as Akt2 mRNA expression in skeletal muscle of rats were detected by glucose oxidase method, ELISA and real-time PCR. Results: Compared with the control group, the level of FPG, FINS and C-P increased significantly (P<0.01) while ISI and Akt2 mRNA expression decreased markedly in the model group (P<0.01, P<0.05). In the acupuncture group, the levels of FPG, FINS and C-P were much lower than in the model group (P<0.01, P<0.01, P<0.05) and ISI and Akt2 mRNA expression increased markedly (P<0.01). Conclusion: The mechanism of acupuncture in treating insulin resistance may relate to the up-regulated of the Akt2 mRNA expression and to the improvement of the signal transduction of PI3K pathway. © 2010 Shanghai Research Institute of Acupuncture and Meridian and Springer-Verlag Berlin Heidelberg.