Objective: To observe and study the influence of external drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage for the serum and cerebrospinal fluid on inflammatory mediators of patients with intracranial infection, in order to understand the clinical application value of the treatment methods. Methods: From June 2016 to May 2018, 56 patients with intracranial infection in the People's Hospital of Lianshui County were selected in the study and randomly divided into two groups according to the random allocation principle, with 28 cases in each group.The control group was treated with repeated lumbar intrathecal drug therapy, the observation group was treated with external drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage.The serum and cerebrospinal fluid inflammatory mediators of two groups before treatment and at the first and second week after treatment were compared. Results: The serum and cerebrospinal fluid inflammatory mediators of the two groups before treatment had no statistically significant differences(all P>0.05). The serum levels of IL-1β, IL-6 and IL-8 of the observation group at the first and second week after treatment were (2.27±0.28)μg/L, (9.25±0.89)μg/L, (11.15±1.35)μg/L and (1.65±0.20)μg/L, (7.04±0.81)μg/L, (8.42±0.79)μg/L, respectively, which were significantly lower than those of the control group [(4.63±0.38)μg/L, (11.92±1.35)μg/L, (14.28±1.75)μg/L and (3.20±0.29)μg/L, (9.41±1.02)μg/L, (11.32±1.47)μg/L] (t=26.456, 8.737, 7.493, 23.282, 9.628, 9.195, all P<0.01). Two weeks after treatment, the levels of IL-1, IL-6 and IL-8 in CSF of the observation group were (1.51±0.15)μg/L, (5.14±0.45)μg/L and (5.96±0.59)μg/L, respectively, which were significantly lower than those of the control group(t=12.876, 12.810, 14.272, all P<0.01). The levels of leukotriene B4(LTB4), substance P(SP) and nitric oxide(NO) in serum and cerebrospinal fluid of the two groups continued to decrease after treatment for one week and two weeks, and those in the observation group were lower than the control group(all P<0.05). Conclusion External drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage can significantly decrease the serum and cerebrospinal fluid inflammatory mediators of patients with intracranial infection, so the treatment method has high clinical application significance.