Abstract. A hierarchy of mathematical models of the mechanism type has been developed. In these models, the complex structure of the right-hand sides of the differential equations reflects the well-known interrelationships of key parameters of the state of a real biological system that determines the biokinetics of the aseptic inflammatory response to damage of any etiology. The hierarchy is a nested sequence of five models obtained as a result of the reduction of a known fairly complete model. The reduction strategy involves a gradual decrease in the dimension of the phase space of states, under the condition that structural and parametric generality and proximity of basic properties of the models are maintained. The models are calibrated using a wide range of experimental time series characterizing the dynamics of in vivo inflammation in excisional skin wounds in mice and several other living models. An important common property of the models is the ability to adequately describe the dynamics of M1/M2 polarization of macrophages, which determines not only inflammation in the wound, but also the subsequent course of the tissue repair process. The robustness of each model is confirmed by the results of two cycles of computational experiments – an analysis of sensitivity to small variations in parameters and a cycle of «diagnostic checks» of the system's behavior in conditions simulating several background pathological conditions known from clinical practice. It is shown that the developed models adequately describe the known scenarios of acute and chronic aseptic inflammation, as well as the fact that due to ineffective efferocytosis, a repeat event in the form of a long, protracted acute process with the possibility of becoming chronic can flare up against the background of an index event of acute inflammation. The results of this investigation provide a wide range of ready-made working tools in the form of cost-effective mathematical models with well-studied properties for studying the dynamics of aseptic inflammation and its management for therapeutic purposes in a wide range of general pathological processes and injuries of various etiologies, for which the innate immune response is an important factor in pathogenesis.