The Serbian has dropped to world No 18 - his lowest ranking in 12 years - having failed to progress past the round of 16 in any of his six events in 2018.
Novak Djokovic got off to a winning start in his bid for a fifth ATP Italian Open title on Monday (May 14) with a straight sets win over Ukraine's Alexandr Dolgopolov as he gears up for the French Open in two weeks time.
Djokovic, who last won in Rome in 2015, next plays either Nikoloz Basilashvili or Filippo Baldi two qualifiers before a potential third round meeting with American eighth seed John Isner.
Nishikori took a one-set lead after a tiebreak.
Djokovic kept the points short and sharp, mixing up his approach expertly and showing no signs of being troubled by his elbow as he broke for a 3-1 lead in the second set with a cross-court victor following another thunderous return.
"Rome has always been a place where I felt good, where I received a lot of support, where I played well, and had a lot of great results", said Djokovic.
But against Dolgopolov, at least, he looked like the 12-time Grand Slam champion of old, breaking three times in the first set and once more in the second to wrap up the routine win. "I feel I'm going in the right direction".
"It is a mental game".
"I have to understand where the level of my game is and to accept this reality and to accept that there is a process to get where I want to go", he said. Knowing that I've reached the biggest heights of this sport and been consistent with the best possible results for so many years.
"Today's match encourages me to move forward and hopefully I can get a few more matches in Rome than I have in the last couple months", said the four-times Italian Open champion.
Vinci bows out Belgian ninth seed David Goffin also eased past Argentine Leonardo Mayer 6-1, 6-2, as Japan's Kei Nishikori sent Feliciano Lopez home early with a 7-6 (7/5), 6-4 defeat-the Spaniard's sixth in seven visits to Rome. "It was windy and he used a lot of slice and great serves". The pair exchanged serves in the second set before 2016 semifinalist Nishikori broke and served out to love to book into the second round against third seed Grigor Dimitrov of Bulgaria.
Spain's Pablo Carreno Busta, the 10th seed, was pushed to three sets by hard-hitting American Jared Donaldson, but held on before flattening his opponent in the decider to win 6-4 3-6 6-0.
Rome - Japan's Kei Nishikori eased into the second round of the ATP Italian Open in Rome on Monday as Italy's Roberta Vinci bowed out of her final WTA tournament with a first-round defeat to a qualifier. "I'm happy for what I've accomplished", Vinci said in a post-match ceremony. "Changes in general are good when they're focused on improvement and that's what I'm focused on and we'll see where it takes me".