Cordyceps sinensis (CS), an Ascomycetes fungus parasitic to Lepidoptera larvae, has been traditionally used as nutritious food for the enhancement in immuno-modulation in Chinese society for a long time. Previous report has demonstrated the CS water extract stimulates in vitro corticosterone production in rat primary adrenal cells. In the present studies, we determined the in vivo effects of CS and its fractions on plasma corticosterone production in mouse. Different concentrations of CS and CS fractions dissolved in water (0.02 and 0.2 mg/g body weight) were fed to immature and mature mice from 1, 3 or 7 d. The plasma levels of corticosterone were determined by radioimmunoassay (RIA), and the weight of adrenal gland and body weight were also evaluated. Results illustrated that plasma corticosterone levels were significantly induced by F2 at 0.02 mg/g body weight with 7 d feeding in immature mice, and by CS at 0.02 mg/g body weight with 3 d feeding and F3 at 0.02 mg/g body weight for 7 d feeding in mature mice, respectively (p < 0.05). There were no differences of adrenal gland weight except there was significant stimulation by CS at 0.2 mg/g body weight with 3 d feeding in mature mice (p < 0.05) and there were significant inhibitions by both dosages of F3 for 3 d feeding in immature mice and F2 for 7 d feeding in mature mice (p < 0.05), respectively. Concerning body weight, the stimulatory effects were observed with CS feeding at 0.2 mg/g body weight for 7 d and F3 feeding at 0.02 mg/g body weight for 3 and 7 d in mature mice. Whereas, the inhibitory effect were observed in F2 feeding at 0.2 mg/g body weight for 7 d in immature mice and at both dosages for 7 d in mature mice, respectively. Taken together, these studies illustrate that CS and its fractions stimulated mouse in vivo corticosterone production. However, CS and its fractions didn't have constant stimulatory or inhibitory effects on the weights of body and adrenal glands.