Fire blight, a disease caused by the bacterium Erwinia amylovora, is a serious threat for pear production worldwide. In order to shed light on the mechanisms underlying fire blight resistance, a comparable study was conducted using 'Dargazi' and 'Duchess', two pear cultivars displaying contrasting responses to fire blight. The activity of ascorbate peroxidase (APX), catalase (CAT), and guaiacol peroxidase (POD) as well as phenylalanine ammonia-lyase (PAL), the enzyme associated with phenolic metabolism, and the relevant biochemical compounds including total phenol and flavonoid contents were compared in two cultivars in response to E. amylovora. All biochemical parameters were affected by pathogen attack. However, the enzymatic responses of resistant and susceptible pear cultivars were completely different following E. amylovora infection. In 'Dargazi' the activity of CAT and APX were significantly suppressed in response to the pathogen attack during the early days after bacterial inoculation, while they were significantly activated in 'Duchess' at the same stages. The POD showed a different pattern of activity from two other antioxidant enzymes. Pathogen attack induced the phenylpropanoid metabolism and caused an increase in PAL activity as well as total phenol and flavonoid content in the two pear cultivars, but a significantly higher rise was recorded in 'Dargazi' than in 'Duchess'. Our data strongly suggest that the hypersensitivity response (HR) may contribute to the high resistance of 'Dargazi' to E. amylovora. Results of present study provide valuable information about the mechanisms underlying the fire blight resistance in 'Dargazi' cultivar which would be highly beneficial for engineering fire blight resistance Pyrus cultivars.