Oral ulcerative mucositis, a common adverse effect due to mainstream cytotoxic drugs, limits the nutritional intake of cancer patients. Rhodiola algida is widely used in traditional Chinese medicine to stimulate the immune system. The aim of this study is to investigate the effect of this herbal extract on healthy human lymphocytes in vitro, the homeostasis of cancer patients and the healing time of oral ulcers. The constituents of Rhodiola algida were analyzed by RP-HPLC. Lymphocytes isolated from 462 healthy subjects were treated with 100 ug/ml Rhodiola algida for 48 h. The activity of the cells was measured by cell proliferation reagent and ATP assay. The level of various cytokines and mRNA content of lymphocytes were determined. Rhodiola algida demonstrated no toxicity in animals, which had been orally fed with 1 mg/ml Rhodiola algida for 30 days. 130 breast cancer patients from Huaxi Hospital of Sichuan University were recruited between 2006 and 2007. They received four cycles of 5-fluorouracil, epirubicin and cyclophosphamide after modified total mastectomy. These patients were randomly assigned to test and control groups. Rhodiola algida mixture was consumed by the test group for 14 consecutive days after each cycle of chemotherapy. All patients were given 0.2% chlorohexidine mouth wash to be used every day. Complete blood counts, liver and renal function tests together with the number and size of oral ulcerations were analyzed after each cycle. Weight loss, complaints of nausea or vomiting and degree of pain were noted. The optimal concentration of Rhodiola algida favored the proliferation of lymphocytes. The levels of IL-2, IL-4, granulocyte-macrophage colony-stimulating factor and the mRNA content of these cytokines were also enhanced. White blood cell (WBC) levels returned to normal range in both groups 1 week after every cycle of chemotherapy. WBC count increased faster in patients using Rhodiola algida; they presented with smaller and fewer oral ulcers. There were no liver or renal complications observed in any patients. Rhodiola algida increases immunity of patients who are receiving chemotherapy post mastectomy and decreases the quantity of oral ulcers. Thus Rhodiola algida has the potential to be used concurrently with chemotherapy to alleviate the occurrence of oral ulcers.