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AIM: To investigate the effect of theophylline on the naive T cell differentiation and the probable role of interleukin12 (IL-12). METHODS: Naive cord blood T cells were treated with theophylline 10 mg/L for 3 d after stimulation with PHA 100 mg/L. Differentiation of T cells was analyzed by flow cytometry. Theophylline 10 mg/L and IL-12-mAb 0.025 mg/L were added in cord blood mononuclear cell (CBMC) cultures primed with LPS 1 mg/L to detect the levels of IL-12 and IL-12P40. The whole blood cultures were obtained from twelve health volunteers with or without administration of theophylline (200 mg). Cytokines were measured by enzyme linked immuno-sorbent assay. RESULTS: Theophylline promoted T helper 1 (Th1) cells differentiation from naive T cells (21.9%±10.3%vs 9.4 %±5.6%, P＜0.05), but had no significant effect on Th2 deviation. But theophylline inhibited the production of IL-12 and IL-12P40 by CBMC in vitro (28±6 ng/L vs 57±14 ng/L and 88±34 ng/L vs 214±82 ng/L, P＜0.01) and reduced IL-12 and IL-12P40 levels in whole blood cultures from healthy subjects (19±11 ng/L vs 31±15 ng/L and 92±13 ng/L vs 196+49 ng/L, P＜0.01). CONCLUSION: Theophylline promoted the differentiation of Th1 cells. IL-12 seemed not to be involved in this process.