Soybean protein has been proposed for distinct applications within nutritional, pharmaceutical, and cosmetic industries among others. More recently, soy-based biomaterials have also demonstrated promising properties for biomedical applications. However, although many reports within other fields exist, the inflammatory/immunogenic potential of those materials is still poorly understood and therefore can hardly be controlled. On the contrary, chitosan (Cht) has been well explored in the biomedical field, either by itself or combined with synthetic or other natural-based polymers. Therefore, the combination of chitosan with soybean protein is foreseen as a suitable approach to control the biological behavior of soy-based biomaterials. Under this context this work was designed to try to understand the influence of chitosan in the host response elicited by soy-based biomaterials. Soybean protein isolate powder (SI-P) and Cht powder (Cht-P) were injected as suspension into the intraperitoneal cavity of rats. SI-P induced the recruitment of higher numbers of leukocytes compared to the Cht-P during the entire observation period. In this sense, SI-P elicited a considerable reaction from the host comparing to the Cht-P, which elicited leukocyte recruitment similar to the negative control. After subcutaneous implantation of the soybean and denatured membranes, (SI-M and dSI-M) a severe host inflammatory reaction was observed. Conversely, Cht/soy-based membranes (Cht/soy-based membranes) showed the induction of a normal host response after subcutaneous implantation in rats, which allowed concluding that the addition of chitosan to the soy-based membranes improved their in vivo performance. Thus, the presented results assert the improvement of the host response, considering inflammatory cells recruitment, and overall inflammatory reaction, when chitosan is combined to soybean. Together with previous results that reported their promising physicochemical characteristics and their inability to activate human polymorphonuclear neutrophils in vitro, the herein presented conclusions reinforce the usefulness of the Cht/soy-based membranes and justify the pursue for a specific application within the biomedical field.