Inbreeding depression (ID), the reduction in fitness of individuals derived from selfing in relation to those derived from outcrossing, is considered a main force driving the evolution of plant mating systems. ID has been detected in many plants traits, and recently it has been documented that plants' natural enemies (e.g., pathogens, herbivores) can affect the magnitude of ID. If inbred individuals show lower resistance to herbivores (and/or pathogens) than outcrossed progenies then herbivores can increase the magnitude of ID, and potentially affect the evolution of the mating system. We examined the effects of inbreeding on resistance to herbivores and fitness traits in the self-compatible plant Datura stramonium. Plants from the population of Teotihuacan were subject to cross- and self-pollinations. A total of seventeen families were used in the experiment. The progenies derived from both pollination treatments were grown in natural conditions, and exposed to herbivores. We estimated ID for survivorship, resistance to herbivores, fruit production, seeds per fruit, and total seed per plant. Significant differences in resistance to herbivores between crossed and selfed progenies were detected (? = 0.05). In addition, ID coefficients for reproductive characters ranged from 0.18 (seeds per fruit) up to 0.40 (total seed number). No differences in survivorship between progenies were detected. The results are consistent with the hypothesis that herbivores can prevent the evolution towards complete selfing.