Introduction. Combinations of polymers of different origins may exhibit improved properties compared to their individual components. However, natural and synthetic polymers can trigger an inflammatory response depending on their molecular weight, chemical purity and route of administration. Polymer combinations may cause more pronounced reactions due to the enhancement of their physicochemical properties. The complete white blood cell count and platelet count are key methods for assessing the body’s inflammatory response to implanted polymer matrices. Purpose. To evaluate blood parameters (leukocyte and platelet profiles) following implantation of innovative polymer matrices in a rat model. Materials and methods. Multilayer polymer films based on chitosan, alginate, pullulan, hyaluronic acid, polyethylene oxide 4000; carboxymethylcellulose and polyvinylpyrrolidone were obtained by solution casting. The study was conducted on 30 male Wistar rats, divided into 5 groups (HCA, KPC, PHC, sham-operated, and control). Film samples were implanted into a subcutaneous pocket in the cervical-thoracic region of the spine. Blood samples were collected on days 0, 21 and 45 to analyze WBC, LY%, GR%, MI%, PLT, MPV, and PDWc. Results. The severity of the response of the rat body was assessed by exploring the leukocyte profile, including WBC, MI%, GR%, and LY%, and platelet parameters PLT, MPV, and PDWc. During the statistical analysis, no statistically significant deviations were found between the five groups for all analyzed parameters at each time point (all values of p_fdr>0.05). It can be assumed that all the samples do not exhibit toxic effects and do not activate an immune response. Conclusion. All tested materials when implanted in rats did not show immune response according blood parameters analysis, i. e. they can be considered biocompatible.