In this work, leucine and glucose were used as model molecules to investigate the Maillard reaction between proteins and carbohydrates during hydrothermal liquefaction (HTL) of microalgae. The main pathway of the Maillard reaction between leucine and glucose via HTL was related to the reaction of deaminated leucine with cyclic oxygenated compounds from degraded glucose to produce pyrazine derivatives. Gas chromatography-mass spectrometry results revealed that N and O heterocyclic compounds, organic acids, and carbonyls/imine/amine were the main components of both the biocrude oil and aqueous fraction. The optimal reaction temperature, reaction time, leucine/glucose weight ratio, and solid concentration for biocrude oil production are 320 degrees C, 60 min, 2:5, and 20 wt %, respectively. The obtained biocrude oil (higher heating value of 38.07 MJ/kg), presenting a large amount of pyrazine derivatives (84.2% peak area), yielded 47.6 wt % of leucine and glucose feedstock.