Danggui Buxue Tang (DBT), a Chinese medicinal decoction that contains Radix Angelicae sinensis (Danggui) and Radix Astragali (Huangqi) at a ratio of 1:5, is used commonly for treating women's ailments. The present study explored the effects of this preparation on chronic fatigue syndrome (CFS). Rats were subjected to a combination of food restriction and forced swimming to induce CFS, and rats were gavaged once daily with either 12 or 24 g/kg DBT for 28 days. Body weights, T-cell subset counts, (3) H-TdR incorporation measurements and mRNA levels of IL-1β, TNF-α, NF-кB, p38MAPK and JNK were determined on days 14 and 28. The swimming endurance capacity was measured on day 28. Rats that received DBT exhibited increased body weight and endurance capacity, corrected T cell subsets counts, increased (3) H-TdR incorporation and decreased mRNA levels of IL-1β, TNF-α, NF-кB, p38MAPK and JNK compared with rats that did not receive DBT. The results indicate that DBT can ameliorate CFS through immune modulation and may act to normalize cytokines and their related signaling pathways.