OBJECTIVE: To observe the effect of electroacupuncture (EA) or manual acupuncture of unilateral or bilateral "Zusanli" (ST 36) on the contents of serum inflammatory factors interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory factors interleukin 2 (IL-2), interleukin 4 (IL-4) and interleukin 10 (IL-10), so as to reveal their mechanism underlying improvement of chronic arthritis. METHODS: Sixty SD rats were randomly divided into normal control, model, electroacupuncture (EA)-left (L) Zusanli (ST 36), EA-bilateral (Bi)-ST 36,and manual acupuncture (MA)-L-ST 36 groups (12 rats/group). Arthritis model was established by subcutaneous injection of complete Freund's adjuvant (0.1 mL)into the hindpaw. EA (2 Hz/100 Hz, 1-3 mA, pulse duration: 0.6 ms/0.2 ms) or manual needle stimulation was applied to the left or bilateral "Zusanli" (ST 36) for 30 min, twice every week for 4 weeks. Enzyme linked immunosorbent assay (ELISA) was used to detect the contents of serum IL-1beta, TNF-alpha, IL-2, IL-4 and IL-10, respectively. RESULTS: Compared with the normal control group, the contents of serum inflammatory factors IL-1beta and TNF-alpha, anti-inflammatory factors IL-4 and IL-10 were increased significantly in the model group (P < 0.001). In comparison with the model group, serum IL-1beta, TNF-alpha, IL-4 and IL-10 contents were down-regulated considerably in the EA-L-ST 36, EA-Bi-ST 36 and MA-L-ST 36 groups (P < 0.001, P < 0.005). Serum IL-2 content had no apparent changes after modeling in comparison with the normal group (P > 0.05). While serum IL-2 contents were markedly higher in the EA-L-ST 36, EA-Bi-ST 36 and MA-L-ST 36 groups than in the model group (P < 0.05). No significant differences were found among the EA-L-ST 36, EA-Bi-ST 36 and MA-L-ST 36 groups in serum IL-1beta, TNF-alpha, IL-2, IL-4 and IL-10 contents (P > 0.05). CONCLUSION: EA or manual acupuncture stimulation of single or bilateral ST 36 can effectively down-regulate serum inflammatory factors IL-1beta and TNF-alpha levels, and upregulate anti-inflammatory factor IL-2 level in chronic arthritis rats, which may contribute to their effects in relieving chronic arthritis.