We study the impact of laser acupuncture with different methods and parameters on type-II collagen-induced arthritis (CIA) model rat serum interleukin-1β (IL-1β), interleukin-15 (IL-15), interleukin-17 (IL-17), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF) and cortisol (COR). The rats are randomly divided into model group, medication group, acupuncture group, deep laser acupuncture 1 mW group, 5 mW group, 10 mW group, the surface laser acupuncture 50 mW group, 100 mW group, 150 mW group, and normal control group is set, selecting Zusanli and Shenshu as acupuncture points. Samples are selected after 10 days of treatment. We use double-antibody enzyme-linked immunosorbent sandwich assay (ELISA) to measure serum cytokine level. Serum IL-1β, IL-15, IL-17, TNF-α and VEGF in the model group are significantly higher than those in the normal group (all P<0.001), and COR is significantly lower than the normal group (P<0.001). IL-1β, IL-15, IL-17, TNF-α and VEGF in all treatment groups after treatment are reduced to different degrees compared with model group, and except individual groups, there are statistical differences (P<0.05, P<0.01, P<0.001); COR in each treatment group is significantly higher than that in the model group (P<0.001). Compared among treatment groups, serum IL-1β level is the highest in the acupuncture group and the lowest in the surface laser acupuncture 50 mW group, and the two have statistical difference (P<0.05); serum IL-15 level is the highest in the acupuncture group and the lowest in the drug group, but the difference is not statistical (P>0.05); serum IL-17 level is the highest in the deep laser acupuncture 1 mW group and the lowest in the surface laser acupuncture 100 mW group, and the difference is statistical (P<0.001); serum TNF-α level is the highest in deep laser acupuncture 1 mW group and the lowest in drug group, and the difference is statistical (P<0.001); serum VEGF level is the highest in deep laser acupuncture 50 mW group and the lowest in the deep laser acupuncture 5 mW group, and the difference is statistical (P<0.05); serum COR level is the lowest in the acupuncture group, and the highest in surface laser acupuncture 150 mW group, the difference is statistical (P<0.001). Laser acupuncture can effectively reduce CIA rat serum proinflammatory cytokines levels such as IL-1β, IL-15, IL-17, TNF-α and VEGF, increase serum anti-inflammatory cytokines levels such as COR, and its effect is related with action mode of laser acupuncture and parameter settings.