Litchi downy blight, a destructive litchi disease caused by
Peronophythora litchii
, is controlled by intensive fungicide applying. Sources of resistance are used in conventional breeding approaches, but the mechanism is not well understood. Follow-up six years investigation, ‘Guiwei’ and ‘Heiye’ displayed stable susceptible and resistant against to
P
.
litchii
, respectively. After 72 hour inoculation, ‘Heiye’ showed few disease spots, while ‘Guiwei’ appeared brown and covered with white sporangia. Germination of sporangia and growth of mycelium in ‘Guiwei’ is more quickly than in ‘Heiye’. Transcript levels were measured at 6, 24, and 48 hour post-inoculation. ‘Oxidation-reduction process’ was dramatically enhanced in ‘Heiye’, which could promote its resistance to pathogen infection. A small ratio (3.78%) of common DEGs indicates that resistant and susceptible cultivars take different strategies to defense against
P
.
litchii
. At early infection stage, ‘Heiye’ induced a larger number of genes, including seven receptor-like kinases, which quickly recognized attack of pathogen and led to a rapidly resistance by regulation of degradation of proteasome, transcription factors, and cell wall remodeling. The early DGEs were exiguous in ‘Guiwei’, suggesting a weak response. Once the infection was successful, the resistance was repressed by down-regulated genes involved in phenylpropanoid metabolism, ET biosynthesis and signaling conduction in ‘Guiwei’. In conclusion, quickly recognition and early responses to pathogen, as well as minimal pathogen development and basal expression of resistance-related genes, were correlated with a high level of resistance in ‘Heiye’, while susceptible ‘Guiwei’ suffered massive infection due to lagging response and repressed signal transduction.