Background: The default mode network (DMN) is closely associated with the maintenance of alertness and cognitive functions. This study aimed to observe the changes in DMN induced by increasing doses of propofol and progressively deepening sedation. Methods: Twelve healthy subjects were selected; they received target-controlled infusion of propofol (1.0 and 3.0 mu g/mL of plasma) and underwent functional magnetic resonance imaging before sedation and when they achieved light and deep sedation states. The average degree, average shortest path length, global efficiency, local efficiency, and clustering coefficient of DMN were assessed to study the overall and internal changes of DMN with gradual changes in alertness level, as well as the relationship between thalamus and DMN. Meanwhile, basic vital signs and respiratory inhibition were recorded. Results: DMN parameters were gradually inhibited with decreasing level of alertness, the differences were significant between light sedation and awake states (all P<0.01), but not between deep and light sedation states. However, the shortest path lengths of the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortexes in the DMN were significantly increased under deep sedation. Conclusion: Overall, DMN is propofol-sensitive. A small dose of propofol can significantly inhibit the DMN, affecting the level of alertness. The posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortexes in the DMN are less sensitive to propofol, and could be significantly inhibited by a higher concentration of propofol, further reducing the level of alertness.