African swine fever virus (ASFV), one of the most devastating emerging swine pathogens in China, causes nearly 100% mortality in naive herds. Here, whole-transcriptome RNA-seq analysis was conducted in porcine alveolar macrophages (PAMs) infected with Pig/Heilongjiang/2018 (Pig/HLJ/18) ASFV in different time points. Our data suggested that ASFV genes expression demonstrated a time-depended pattern and ASFV early genes were involved in antagonized host innate immunity. Moreover, viral small RNA (vsRNA) was generated as well. Meanwhile, transcriptome analysis of host genes suggested a strong inhibition host immunity-related gene by ASFV infection in PAMs, while enhanced chemokine-mediated signaling pathways and neutrophil chemotaxis were observed in ASFV infected PAMs. Furthermore, ASFV infection also down-regulated host miRNAs that putatively targeted viral genes, while also triggering dysregulation of host metabolism that promoted virus replication at transcription level. Most importantly, infection of PAMs with ASFV induced a different transcriptome pattern from that of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), which is known to trigger a host cytokine storm. In conclusion, our transcriptome data implied that ASFV infection in PAMs appeared to be associated with strong inhibition of host immune responses, dysregulation of host chemokine axis and metabolic pathways.