The article discusses the research results on the combustion of pyrolysis oil derived from the pyrolysis of HDPE plastics after its distillation. The tests were carried out in a constant-volume combustion chamber in conditions similar to those in a compression-ignition engine with a compression ratio of 17.5:1. The phases of premixed and diffusion combustion and the ignition lag were determined. Diesel fuel combustion tests were performed under similar pressure-temperature conditions. Comparative analysis was used to draw conclusions as follows: the duration of the premixed combustion phase for pyrolysis oil is approximately 5% shorter than that for diesel oil; with an increase in the initial pressure in the chamber, the premixed combustion time in both cases was shortened, while the diffusion combustion time slightly increased, practically without any significant change; the maximum combustion rate for the premixed combustion phase for pyrolysis oil was nearly 20% higher than that for diesel fuel; the heat released from the premixed combustion phase for pyrolysis oil was found to be 20% higher compared to that one for diesel fuel; the ignition lag for pyrolysis oil was slightly longer compared to that for diesel fuel. The presented parameters significantly impact both the development of combustion and the thermal efficiency of the internal combustion engine. Summing up, pyrolysis oil can be applied as a substitute for diesel fuel as a single or blended component with it.