Objective: To investigate the effects of Ganoderma lucidum spores (GLS) on NOD mice –a spontaneous animal model of Sjögren's Syndrome (SS). Methods: Twenty-four 10-week NOD and 24 matched BALB/c mice were divided randomly as 4 groups respectively: high (1g· kg
-1·d
-1), low–dosage (0.1g·kg
-1·d
-1) of GLS treatment group, 5mg· kg
-1·d
-1 dexamethasone control and negative (water) control group. Stimulated total saliva flow rate (TSFR) and ratios of CD4
+ T, CD8
+ T subsets and B cell in peripheral blood lymphocytes (PBLs) as well as apoptosis of these cells were tested by flow cytometry after 10 weeks of treatment. Results were analyzed by analysis of variance (ANOVA) of SPSS11.5. Results: TSFR , CD4
+ T /CD8
+ T and late stage of B cells apoptosis decreased significantly , while apoptosis of CD4
+T and CD8
+ T increased obviously in NOD mice compared with control BALB/c mice (p<0.05). After treatment, compared with negative control group, CD4
+ T and CD8
+ T apoptosis decreased significantly in NOD mice of low dosage GLS group (p<0.05), TSFR and late stage of B apoptosis increased. TSFR increased obviously in DEX group (p<0.05), while LC percentage and CD4
+ T /CD8
+ T decreased significantly with increasing late-stage apoptosis of CD4
+ T, CD8
+ T and B of PBLs (p<0.05). Conclusion: These results indicate that immunodysregulation in NOD mice is increase of CD4
+ T, CD8
+ T apoptosis and decrease of B lymphocytes apoptosis, GLS modulates these changes in bidirectional ways. Effects of GLS on NOD mice are different from those of DEX.