Objective To explore the effect of systemic low-level light therapy (LLLT) on early inflammatory response of severe burn rats. Methods Fifty SD rats were randomly divided into control group, burned model group, single short-term LLLT group, single long-term LLLT group and the repeated short-term LLLT group, with 10 rats in each group. After burning the rats in the single short-term LLLT group, the single long-term LLLT group and the repeated short-term LLLT group were treated by low-intensity LED irradiation (640 nm) for 5 min once a day, 15 min once a day and 5 min three times a day, respectively.The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 and the leukocyte count in caudal vein were determined at 1 day before modeling, immediately after modeling and on the 1^st, 3^rd, 7^th and 14^th day after modeling; and the wound area was measured on the 3^rd, 7^th and 14^th day after modeling. The wound healing rate was calculated. Results Compared with the control group, the serum TNF-α levels in the burned model and single short-term LLLT groups were significantly increased on the 1^st day after modeling (P<0.05), and the serum TNF-α levels in the single long-term LLLT group on the 1^st day and the repeated short-term LLLT group on the 7^th day were significantly increased (P<0.05); the serum IL-1β levels were significantly decreased on the 1^st day after modeling in all groups (P<0.05), and then gradually recovered with the varied recovery rates; the serum IL-6 levels in the burned model and the repeated short-term LLLT groups were significantly increased on the 1^st day after modeling (P<0.05), then decreased; and the decrease of the burned model group was greater than that of the repeated short-term LLLT group. While the serum IL-6 level was increased on the 3^rd day in the single short-term LLLT group, then decreased; and the level was significantly increased in the single long-term LLLT group (P<0.05). Leukocyte counts of the burned model and the single long-term LLLT groups were significantly increased on the 1^st day after modeling (P<0.05), and it had no significant change in the other groups. The wound healing rate in the single short-term LLLT group, the single long-term LLLT group and the repeated short-term LLLT group was significantly higher than that in the burned model group (P<0.05). Conclusion Systemic LLLT use can reduce the serum levels of TNF-α, IL-1β and IL-6 and leukocyte count in caudal vein of the severe burning rats and promote wound healing, with the effects varied with different irradiation modes.