Objective: To investigate the therapeutic effect of minimally invasive catheter drainage on early inflammatory response of severe acute pancreatitis (SAP). Methods: Fifty-seven SAP patients with peritoneal effusion were divided into the observation group (29 cases with minimally invasive catheter drainage) and control group (28 cases with conventional drainage) using a random number table. Both groups underwent the same basic regimen of treatment, and then the observation group received the minimally invasive drainage while the control group had conventional ultrasound-guided catheter drainage. The inflammatory indexes responding to acute inflammatory such as TNF-α, IL-6, IL-8 and CRP were detected before and after treatment. Meanwhile, the recovery time of bowel function, and duration of systemic inflammatory response syndrome (SIRS) and incidence of multiple organ dysfunction syndrome (MODS) were observed. Results: The acute inflammatory response occurred in the both groups, and all the serum inflammatory indexes detected in the both groups tended to gradually decrease with different degrees. The levels of TNF-α, IL-6 and CRP on day 3 and 7, and the level of IL-8 on day 7 after drainage in the observation group were significantly lower than those of the control group (all P<0.05). The recovery time of bowel function and the SIRS duration of the observation group were shorter than those of the control group (both P<0.05). Furthermore, the incidence of MODS of the observation group (13.8%) was also significantly lower than that of the control group (28.6%) (P<0.01). Conclusion: Minimally invasive catheter drainage for SAP can lessen the early inflammatory response, accelerate bowel function recovery, and reduce the incidence of MODS.