We hypothesized that steam-flaking the high-starch grains can stimulate ruminal microbial activity and reduce cecal fermentation due to lowering starch escaping in to hind-hut of young calves. Therefore, the current study evaluated the effect of steam-flaking the grains (corn grain vs. barley grain) with either 18% (18CP) or 22% (22CP) dietary protein content (dry matter basis) on growth performance, microbial protein synthesis (MPS) and inflammatory markers in young calves. Female Holstein calves (48 calves with 3 d of age) were assigned randomly to the following treatments: SFC-18CP, SFC-22CP, SFB-18CP, and SFB-22CP (n = 12, each). Milk feeding schedule was identical among treatments until weaning (d 53), and calves had ad-libitum access to water and starters until the final day of experiment (d 73). Feeding SFC increased starter intake compared to calves fed SFB diet (p = 0.05; pre-weaning, have greater feed efficiency (tendency, p = 0.07; post-weaning), better fecal score (p = 0.01), and higher hip height (p = 0.03; post-weaning) compared to calves fed SFB diet. However, ruminal pH was lower (p = 0.04; pre-weaning), heart girth was smaller (p = 0.02), and post-weaning circulating tumor necrosis factor-α was greater (TNF-α, p = 0.03) for calves fed SFB compared to calves fed SFC diet. Feeding 22CP compared to 18CP diet improved hip height at weaning time (p = 0.01) and reduced pre-weaning serum amyloid A (SAA, p = 0.04). With respect to the interaction, results indicated that higher ADG (p = 0.04) and subsequently higher BW (p < 0.05) was detected for calves fed SFC along with 22CP diet compared to other experimental arranegemnets. The calves fed SFB along with 18CP diet had lower withers height (p = 0.01), lower urinary allantoin (p = 0.02), and MPS (p = 0.04); but higher TNF-α (p = 0.01; pre-weaning) and higher SAA (p = 0.04; post-weaning) was found to be for SFB-18CP diet compared to other experimental treatments. Based on the results obtained in the current study, feeding SFC can be more favoable diet than SFB diet in young calves due to improve ruminal microbial activity and more faborable immune function. Furthermore, results suggest that feeding steam flaked corn grain with 22CP diet had positive interaction resulted in higher microbial protein production and growth performance of young calves. Optimal processing method applied for high-starch grains to increase ruminal fermentation and prevent starch escaping in to the hind-gut of young calves for reducing cecal fermentation needs to be more evaluated in milk-fed calves.